This research project proposes to identify the mechanisms of death in severely injured man and to develop therapeutic maneuvers that prevent or reverse the operative mechanisms. In the presence of continued vigorous cardiopulmonary support, the most common set of circumstances surrounding death may be most briefly summarized as multiple systemic organ failure. This is associated with a systemic circulatory failure characterized overall as systemic arteriovenous shunting like behavior that has asssociated with it reduced oxygen consumption because of a failure of oxygen extraction, hyperglycemia, hypertriglyceridemia, high plasma fatty acids relative to the glucose, and increased concentrations of all amino acids relative to the branched chain amino acids which themselves may be reduced, normal or increased depending upon exogenous support. Associated with these observations are reduced protein synthesis relative to demand and intolerance to infused glucose, intralipid, and all amino acids except the branched chains. These characteristics are associated with a reduced hypoglycemic effect from insulin and with clear cut enhanced catabolism of albumin and probably several other proteins including especially muscle protein. These associated disorders appear to have as a basic mechanism reduced peripheral utilization of glucose and fatty acids as oxidative fuel in association with enhanced obligatory amino acid oxidation. The research is based upon determining by organ studies, the mechanism of the enhanced amino acid oxidation.